It is the long range plan of this project to evaluate actions of receptors for toxic halogenated aromatics and estrogenically-active chemicals in relation to hepatotoxic potency of these compounds. These studies focus on receptor mediated effects on gene expression critical to tumor promotion using the rat two-stage model for hepatocarcinogenesis. The compounds of special interest are 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD), structurally-related polychlorinated dibenzodioxins and dibenzofurans, diethylstilbestrol, 17Alpha-ethinylestradiol and Alpha-zearalanol. The objectives of these studies are to evaluate the quantitative relationships between dose of tumor promoter, receptor occupancy, critical changes in gene expression and histopathological alterations including preneoplastic lesions and tumor incidence. Furthermore, the time course of these changes are being investigated.